TABLE 2.

Putative protein biomarkers and their differential expression in distinct SALS patient subgroups.

					Gene expression in SALS motor cortex*
Biomarker symbol	Biomarker name	CSF/Serum/Plasma	Prognostic/Diagnostic value	References	SALS1	SALS2
Neuron specific
MAPT	Microtubule-associated protein tau	CSF	Disease progression	(164)	↑	↓
NEFH	Neurofilament, heavy polypeptide	CSF	Diagnosis and progression	Rosengren et al., 2002; Brettschneider et al., 2006	–	↓
NEFM	Neurofilament, medium polypeptide	CSF	Diagnosis and progression	Rosengren et al., 2002	–	↓
NEFL	Neurofilament, light polypeptide	CSF	Diagnosis and progression	Rosengren et al., 2002; Zetterberg et al., 2007	–	↓
Hormones and growth factors
VEGFA	Vascular endothelial growth factor A	CSF	Diagnosis and progression	Moreau et al., 2006; Pasinetti et al., 2006; Zhao et al., 2008	–	↓
GDNF	Glial cell-line derived neurotrophic factor	CSF	Diagnosis	Tanaka et al., 2006	↓	↑
IGFBP-2	Insulin-like growth factor binding protein 2	Plasma, Serum	Diagnosis and progression	Hosback et al., 2007	–	↓
IGFBP-3	Insulin-like growth factor binding protein 3	Plasma, Serum	Diagnosis and progression	Hosback et al., 2007	↑	↑
IGFBP-5	Insulin-like growth factor binding protein 5	Plasma, Serum	Diagnosis and progression	Hosback et al., 2007	↑	↓
FGF-2	Fibroblast growth factor 2	CSF, Serum	Diagnosis	Johansson et al., 2003	–	↓
HGF	Hepatocyte growth factor	CSF	Diagnosis	Tsuboi et al., 2002	–	↓
Inflammatory system related
IL2	Interleukin 2	CSF	Diagnosis	Mitchell et al., 2009	–	↑
IL4	Interleukin 4	CSF, Plasma	Diagnosis and progression	Furukawa et al., 2015	–	↑
IL5	Interleukin 5 (colony-stimulating factor, eosinophil)	Plasma	Diagnosis	Lu et al., 2016	–	↑
IL6	Interleukin 6 (interferon, beta 2)	CSF, Plasma	Diagnosis and progression	Bilic et al., 2006; Mitchell et al., 2009	–	↓
IL-10	Interleukin 10	CSF, Plasma	Diagnosis and progression	Mitchell et al., 2009; Furukawa et al., 2015; Andrés-Benito et al., 2017	–	↓
IL-13	Interleukin 13	Plasma	Diagnosis and progression	Shi et al., 2007; Lu et al., 2016	–	↑
IL-15	Interleukin 15	CSF, Plasma	Diagnosis	Mitchell et al., 2009	–	↓
TNF	Tumor necrosis factor-alpha	CSF, Plasma	Diagnosis	Andrés-Benito et al., 2017	↓	–
TNFRSF1A	Tumor necrosis factor receptor superfamily, member 1A	Serum, Plasma	Diagnosis	Andrés-Benito et al., 2017	–	↓
IFNG	Interferon, gamma	CSF, Plasma	Diagnosis and progression	Guo et al., 2017	↓	↑
TGFB1	Transforming growth factor beta 1	Plasma	Disease progression	Duque et al., 2020	–	↑
GFAP	Glial fibrillary acidic protein	CSF	Diagnosis	Benninger et al., 2016	↑	–
CXCL10	Chemokine (C-X-C motif) ligand 10	CSF	Diagnosis and progression	Tateishi et al., 2010	↓	–
Enzymes and enzyme inhibitors
CST3	Cystatin C	CSF	Diagnosis	Ranganathan et al., 2005	↑	–
MMP2	Matrix metallopeptidase 2 (gelatinase A, 72 kDa gelatinase, 72 kDa type IV collagenase)	CSF, Plasma	Diagnosis	Niebroj-Dobosz et al., 2010	–	↑
MMP9	Matrix metallopeptidase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase)	CSF, Serum, Plasma	Diagnosis	Beuche et al., 2000; Lorenzl et al., 2002	–	↓
TIMP1	TIMP metallopeptidase inhibitor 1	CSF, Serum, Plasma	Diagnosis	Lorenzl et al., 2002; Niebroj-Dobosz et al., 2010	↑	↑
SOD1	Superoxide dismutase 1, soluble	CSF, Plasma	Diagnosis	Jacobsson et al., 2001	–	↓
CHIT1	Chitinase 1 (chitotriosidase)	CSF	Diagnosis and progression	Thompson et al., 2018	–	↑
Others
TARDBP	TAR DNA binding protein	CSF	Diagnosis	Majumder et al., 2018; Kasai et al., 2019	–	↓
S100B	S100 calcium binding protein B	CSF	Disease progression	Süssmuth et al., 2003	–	↓

↑, Concentration increased in SALS patients compared to controls; ↓, Concentration decreased in SALS patients compared to controls. *Aronica et al. (2015).